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Phase 2 Metabolic > Haematological Malignancy > Flashcards

Haematological Malignancy Flashcards

1
Q
  1. which cells are malignant in Malignant Myeloma?
  2. What is the biomarker of this malignancy?
    a) in the serum
    b) in the urine
A
  1. BONE MARROW PLASMA CELLS
  2. para protein
  3. bence jones protein (urinary excretion of light chains)
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2
Q
  1. what is the mean age of presentation of malignant myeloma?
  2. in which groups is malignant myeloma more common?
A
  1. 60+

2. males and those of african descent

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3
Q

Describe the clinical features (and the pathophysiology as to why they happen) of malignant myeloma (4)

A
  1. BONE PAIN, PATHOLOGICAL FRACTURES, SPINAL CORD COMPRESSION, HYPERCALCAEMIA
    - bone lesions with increased osteoclast activity results in bone destruction
  2. PANCYTOPENIA (infection, anaemia, bleeding) - due to bone marrow infiltration of plasma cells
    - thrombocytopenia + paraprotein = hyperviscosity
  3. KIDNEY INJURY
    - deposition of light chains in renal tubiles
    - hypercalcaemia
    - hyperuricaemia (high cell turnover)
    - use of NSAIDs with pain
  4. RECURRENT INFECTION
    - neutropenia
    - reduction in normal Ig levels
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4
Q

Name 4 life threatening complications of malignant myeloma (and how they are managed)

A
  1. renal impairment (may require renal replacement therapy)
  2. hypercalcaemia (rehydration and bisphosphonates)
  3. malignant spinal cord compression (radiotherapy within 24 hrs and dexamethasone)
  4. hyperviscosity (corrected with plasmapheresis)
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5
Q

What investigations should you perform for ?malignant myeloma?

A
  1. FBC (Hb, WCC, platelets normal or low)
  2. ESR (often raised)
  3. blood film
  4. U&E (may demonstrate evidence of kidney injury)
  5. Serum Ca
  6. serum protein electrophoresis - presence of paraprotein
  7. urine electrophoresis - presence of bence jones protein
  8. bone marrow aspirate and biopsy - definitive test for MM
  9. whole body MRI
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6
Q

What is MGUS?

A

monoclonal gammopathy of unknown significance:
- isolated serum paraprotein that does meet diagnostic criteria for symptomatic or asymptomatic myeloma.
20-30% will progress to multiple myeloma in a 25 yr period

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7
Q

Describe the specific therapy for malifnant myeloma

A
  1. alkylating agent - cylophosphamide or melphalan
  2. steroid (pred or dex)
  3. novel agent - bortezomib or thalidomide
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8
Q
  1. Why are cancers arising from less mature cells more aggressive?
  2. Why are cancers arising from more mature cells less aggressive?
A
  1. the main role of these cells is to divide - more likely to cause an acute cancer
  2. the proliferative capacity of these cells is diminished as they have differentiated. More likely to cause chronic cancer
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9
Q

What do the following terms usually mean:

  1. leukaemia
  2. -oma
A
  1. presence of abnormal cells in the peripheral blood

2. solid mass. No abnormal cells in the peripheral blood

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10
Q

What is the classical presentation of leukaemia related to?

A

PANCYTOPENIA secondary to bone marrow failure

  • anaemia - reduction in RBC
  • recurrent infection - reduction in WBCs
  • bleeding - reduction in platelets
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11
Q

Why do acute malignancies demonstrate a quicker/more effective response to cytotoxic agents?

A

as the malignant cells are rapidly dividing

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12
Q
  1. Why cant a bone marrow autograft be performed for acute malignancies?
  2. How is a bone marrow autograft performed?
  3. Why must a patient have a good performance status for a bone marrow transplant?
A
  1. involves replacing bone marrow with early progenitors; in acute malignancies, it is these early progenitors that are malignant
  2. conditioning chemo and growth factors are given; this stresses the bone marrow which produces more cells as a response; early progenitors spill over into peripheral blood, thus can be harvested
    total body irradiation to kill bone marrow prior to transplant
  3. total body radiation is a radical treatment
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13
Q
  1. What are B symptoms caused by?
  2. Give examples of B symptoms
  3. Which drug can be useful in managing debilitating B symptoms?
A
  1. acute inflammatory response against malignancy
  2. fever, night sweats, weight loss
  3. Thalidomide
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14
Q
  1. Which leukaemia is more common in childhood?

2. Which leukaemia is a disease of the elderly?

A
  1. ALL

2. CLL

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15
Q

Name 4 risk factors associated with the development of leukaemia

A
  1. radiation exposure
  2. chemicals and drugs - benzene, alkylating agents, topoisomerase inhibitors
  3. genetic factors
  4. viral infection
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16
Q

What are the consequences of high WCC in acute leukaemias?

A

Leukostasis - accumulation of WBC aggregates in blood vessels which impede blood flow

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17
Q

What are the consequences of substance release from leukaemic cells?

A
  • disseminated intravascular coagulation

- hyperuricaemia

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18
Q

What is the name given to the immature myeloid/lymphoid precursors in acute leukaemia?

A

Blast cells (myeloblasts or lymphoblasts)

19
Q
  1. Which investigations are useful in a patient with ?acute leukaemia?
  2. Which tests are useful in planning therapy for a patient with leukaemia?
A 
1. blood count - pancytopenia
    blood film - presence of blast cells
    bone marrow aspirate
    CXR - mediastinal widening
    CSF examination
    coagulation profile (to exclude presence of disseminated intravascular coagulation)
  1. U&E, LFT, serum urate
    cardiac function
    HLA type
20
Q

Describe the chemotherapy regime for ALL

  1. Remission induction
  2. Consolidation
  3. CNS prophylaxis
  4. Maintenance
A
  1. vincristine, prednisolone, L-asparaginase and daunorubicin
  2. daunorubicin
  3. methotrexate ± CNS irradiation
  4. mercaptopurine, methotrexate, vincristine and prednisolone for 2 years
21
Q
  1. What type of bone marrow transplant can be given for acute leukaemia?
  2. How is this performed?
  3. Name 4 complications of bone marrow transplant
A
  1. allograft
  2. Pluripotent haematopoietic stem cells are collected from bone marrow and HLA matched to donors on database
    Chemotherapy + whole body radiation is performed to destroy leukaemic cells (+ rest of bone marrow) and then bone marrow is repopulated with infused donor cells
  3. opportunistic infection, relapse of leukaemia, infertility, graft v host disease
22
Q
  1. What is the genetic hallmark of CML?
  2. what is the timecourse of CML?
  3. What can CML progress to if not initially cured?
A
  1. Philadelphia chromosome - BCR-ABL fusion protein
  2. slow, progressive course
  3. blast crisis (transformation to acute leukaemia)
    myelofibrosis
23
Q

Name some symptoms associated with CML

A 
1. symptomatic anaemia
   abdominal discomfort attributed to splenomegaly
   weight loss
   fever and night sweats
   headache
   bleeding and bruising
24
Q

How is CML managed?

A

Imatinib!

25
Q
  1. What does CLL result from?

2. How does the disease present?

A
  1. clonal expansion of small B lymphocytes which are functionally incompetent
  2. majority of patients are asymptomatic and disease is detected incidentally
    - some patients present with features of marrow failure
26
Q
  1. What is the finding of bone marrow aspiration in CLL?
  2. What staging is used for CLL?
  3. How is CLL managed?
A
  1. heavily infiltrated with lymphocytes
  2. Rai and Binet Staging
  3. often managed with watchful waiting. Patients treated if they develop symptoms
27
Q

How do patients with lymphoma commonly present?

A
  • peripheral lymphadenopathy
  • B symptoms
    • weight loss
    • fever
    • sweats
28
Q
  1. Which diagnostic test is used to confirm diagnosis of lymphoma?
  2. Which other tests are useful in the investigation of lymphoma?
  3. Which tests are used to plan specific therapy?
A
  1. excision biopsy of relevant tissue with histological, immunological and molecular analysis
    • CXR to examine for mediastinal widening
    • CT TAP and PET for staging
    • bone marrow biopsy (for stage III/IV disease/HIV+ patients/patients with B symptoms)
3. U&E, LFTs
    serum uric acid (risk of tumour lysis syndrome)
    virology (HIV, Hep B and C)
    Cardiac function
    Respiratory function
    Fertility
29
Q
  1. What is the gender predominance of hodgkin’s lymphoma?

2. At what age is the incidence of hodgkin’s lymphoma highest?

A
  1. more common in males

2. third decade of life

30
Q

Name 2 infections which increase risk of Hodgkin’s Lymphoma

A
  1. EBV

2. Infectious mononucleosis

31
Q

What histology is characteristic of:

  1. Classical Hodgkin’s Lymphoma?
  2. Non-classical Hodgkin’s Lymphoma?
A
  1. REED STERNBERG CELL

2. Popcorn cell (variant of Reed Sternberg)

32
Q

Describe clinical features of Hodgkin’s Lymphoma

A
  • painless lymphadenopathy (usually cervical)
  • cough (due to disease of the mediastinum)
  • hepatosplenomegaly
  • B symptoms
33
Q

Describe the Ann Arbor Staging used in Hodgkin’s Lymphoma

A
  1. involvement of SINGLE lymph node/lymphoid structure/extranodal site
  2. involvement of ≥2 lymph nodes or involvement of only one extranodal organ and lymph node region ON THE SAME SIDE OF THE DIAPHRAGM
  3. involvement of lymph node regions on BOTH SIDES OF THE DIAPHRAGM or localised involvement of only one extranodal site
  4. diffuse or disseminated involvement of ≥1 extra nodal organs/tissues with or without associated lymph node involvement
34
Q

Name the 4 unfavourable prognostic factors associated with Hodgkin’s Lymphoma

A
  1. 3+ sites of disease
  2. bulky mediastinal disease
  3. elevated ESR
  4. extranodal extension
35
Q

How is Hodgkin’s Lymphoma managed?

A

ABVD chemotherapy + involved field irradiation

  • Doxorubicin
  • Bleomycin
  • Vinblastine
  • Decarbazine
36
Q

Which types of Non-Hodgkin’s lymphoma are more common?

A

B cell NHLs

37
Q

Name 4 risk factors associated with the development of Non-Hodgkin’s Lymphoma

A
  1. family hx
  2. Infection
    • Human T cell leukaemia virus
    • H pylori (extra nodal lymphoma of the stomach)
    • chlamydia (MALT lymphoma)
    • EBV (Burkitt’s Lymphoma)
  3. inherited syndromes
  4. immunosuppression
38
Q
  1. Describe the pathogenesis which leads to the different subtypes of Non Hodgkin’s lymphoma?
  2. How are Non Hodgkin’s Lymphomas classified?
A
  1. malignant clonal expansion of lymphocytes occurring at different stages of lymphocyte development
  2. based on their cell of origin and the stage of lymphocytic maturation at which they develop?
39
Q
  1. Which NHL is the most common adult lymphoma worldwide and second most common lymphoma in childhood?
  2. Which NHL is the second most common NHL?
  3. Which NHL is the most common childhood malignancy worldwide?
A
  1. Diffuse Large B lymphoma
  2. Follicular lymphoma
  3. Burkitt’s Lymphoma
40
Q

Name 3 types of B cell NHLs which are aggressive

A
  1. Diffuse Large B cell lymphoma
  2. Follicular Lymphoma
  3. Bukitt’s Lymphoma
41
Q

Name the 3 types of Burkitt’s Lymphoma

A
  1. Endemic - associated with EBV
  2. Sporadic (30% are EBV related)
  3. AIDS related
42
Q

How are B cell NHLs treated?

A

R-CHOP

  • Rituximab
  • cyclophosphamide
  • doxorubicin
  • vincristine
  • prednisolone
43
Q
  1. What is the MOA of rituximab?

2. Why is it only used to treat B cell NHLs and not T cell?

A
  1. Monoclonal antibody which targets CD-20 expressed on almost all B cell lymphomas
  2. CD20 is not expressed on T cells

Phase 2 Metabolic (12 decks)

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